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The molecular basis for public T-cell responses?

Nature Reviews Immunology volume 8, pages 231–238 (2008)Cite this article

Abstract

Public T-cell responses, in which T cells bearing identical T-cell receptors (TCRs) are observed to dominate the response to the same antigenic epitope in multiple individuals, have long been a focus of immune T-cell repertoire studies. However, the mechanism that enables the survival of a specific TCR from the diverse repertoire produced in the thymus through to its involvement in a public immune response remains unclear. In this Opinion article, we propose that the frequency of production of T cells bearing different TCRs during recombination has an important role in the sharing of TCRs in an immune response, with variable levels of 'convergent recombination' driving production frequencies.

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Figure 1: Schematic illustration of convergent recombination.
Figure 2: The relationship between the number of individuals in which a T-cell receptor (TCR) sequence is present and the number of copies of that TCR sequence in the individuals.
Figure 3: An illustration of the uneven landscape of T-cell receptor recurrence and how this leads to public and private T-cell responses.

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Acknowledgements

We thank A. Collins and R. Ribeiro for reviewing the manuscript and for helpful discussions, and K. Kedzierska, S. Turner and P. Doherty for provision of the mouse TCR data, which initially motivated our interest in TCR sharing, and for helpful discussions. This work was supported by the James S. McDonnell Foundation 21st Century Research Award/Studying Complex Systems, the National Institutes of Health, the Australian National Health and Medical Research Council, and the Australian Research Council. M.P.D. is a Sylvia and Charles Viertel Senior Medical Research Fellow. D.A.P. is a Medical Research Council (UK) Senior Clinical Fellow.

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Authors and Affiliations

  1. Vanessa Venturi and Miles P. Davenport are at the Complex Systems Biology Group, Centre for Vascular Research, University of New South Wales, Kensington New South Wales 2052, Australia.,

    Vanessa Venturi & Miles P. Davenport

  2. Daniel C. Douek is at the Human Immunology Section, Vaccine Research Center, NIAID/NIH, Bethesda, Maryland 20892, USA.,

    David A. Price & Daniel C. Douek

  3. and the Department of Medical Biochemistry and Immunology, David A. Price is at the Human Immunology Section, Vaccine Research Center, NIAID/NIH, Bethesda, Maryland 20892, USA, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.,

    David A. Price

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Correspondence to Daniel C. Douek or Miles P. Davenport.

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Supplementary information

Supplementary information S1 (figure)

Schematic illustration of convergent recombination. (PDF 764 kb)

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FURTHER INFORMATION

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Glossary

Clonal dominance

The dominance of a particular clonotype over others involved in an immune response to a specific epitope. This clonotype will be found at a higher copy number in the responding T-cell receptor (TCR) repertoire than other clonotypes.

Convergent recombination

The process whereby multiple recombination events 'converge' to produce the same nucleotide sequence and multiple nucleotide sequences 'converge' to encode the same amino-acid sequence. This process enables some TCR sequences to be produced more frequently than others.

Private T-cell response

An immune response to a specific epitope involving predominantly T cells bearing TCRs that are rarely observed in multiple individuals.

Public TCR

A TCR that is present and dominant in immune responses to a specific epitope in a majority of individuals.

Public T-cell response

An immune response to a specific epitope involving predominantly T cells bearing TCRs that are frequently observed in multiple individuals.

TCR recurrence

A measure of the average production frequency of a TCR. That is, the average number of copies of a TCR sequence per individual produced by V(D)J recombination.

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Venturi, V., Price, D., Douek, D. et al. The molecular basis for public T-cell responses?. Nat Rev Immunol 8, 231–238 (2008). https://doi.org/10.1038/nri2260

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